Anticancer drugs (ACD) are generally known to be immunosuppressive. Recently, some of these drugs have been shown to modulate immune responses in animal studies. If the mechanisms by which ACD stimulate, suppress or restore immune effector mechanisms are better understood, it would be possible perhaps to manipulate treatments so that the effectiveness of a drug can be increased without deleterious effects. The objectives of this study are to understand the mechanisms involved in the ACD associated increase or decrease of spontaneous and induced cell mediated cytotoxicity (CMC) against human autologous or allogeneic leukemic cells, generate murine leukemic specific cytotoxic lymphocytes, grow them in long term cultures and then assess the biological importance of the cytotoxic cells. In vitro immunization system and in vivo syngeneic murine tumor models will be employed to accomplish the following specific aims: 1. Immunomodulation of CMC to leukemia cells by anticancer drugs: a) effect of ACD on in vitro lymphocyte survival, lymphocytes from cancer patients or normal persons will be treated with different concentrations of ACD and the viability of treated cells will be determined, b) stimulation of lymphocyte proliferation by ACD; lymphocytes will be treated with different concentrations of ACD, transformation into lymphoblasts will be measured by 3H thymidine incorporation, c) effect on CMC; lymphocytes will be incubated with different concentrations of ACD, cytotoxicity of treated cells will be tested against 51CR-ALB, d) Characterization of cytotoxic cells in ACD treated cells; the nature of ACD-modulated cells will be determined and e) suppression of CMC by ACD; the mechanisms by which ACD suppress the CMC will be determined. 2. Adoptive chemo-immunotherapy: Established tumors will be tested with, a) non-immune cells, b) in vitro immunized cells, and c) tumor specific cytotoxic cells growing as long term continuous cultures, as adjunct to chemotherapy.